This is a renewal application for a NIDA Independent Scientist Award (K02). The candidate, Amelia J. Eisch, Ph.D., is a tenured Associate Professor in the Department of Psychiatry at UT Southwestern Medical Center. Dr. Eisch is a pioneer in understanding the reciprocal relationship between certain forms of hippocampal plasticity such as adult hippocampal neurogenesis and behaviors relevant to addiction. The first award period of this K02 provided Dr. Eisch with the protected time she needed to accomplish her past goals, which included renewing her NIDA R01 grant on opiates and neurogenesis, securing additional federal funding, advancing her work from correlative to more mechanistic and causative studies, and being promoted to Associate Professor and receiving tenure. This K02 renewal is requested in order to continue this protected time and to allow Dr. Eisch to utilize the momentum she has established in understanding the proposed reciprocal role between new neurons in the adult brain and addiction. The receipt of a K02 renewal award would allow her continued protection from administrative burdens, and thus allow Dr. Eisch to advance: (1) research on the relationship between adult-generated neurons and behaviors relevant to addiction; (2) dissection of the cellular, molecular, and genetic control of adult-generated hippocampal neurons; (3) newly developed collaborations on translational profiling, ultrastructural analysis, and circuit-level impact of new neurons; (4) application of new techniques for these collaborations (BAC-TRAP, optogenetics, EM, electrophysiology); (5) data collection for grant applications: the 10-year renewal of her existing R01 on opiates and neurogenesis, a new NIDA R01 relevant to the molecular control of hippocampal neurogenesis, and a new NIDA R01 relevant to behavioral and circuit-level impact of adult-generated neurons. By providing this protected time, Dr. Eisch can work closely with her collaborators and rapidly advance her new ideas, thus benefitting the fields of addiction research and stem cell biology and neuroscience as a whole. The stability and protected time offered by this K02 award would ultimately support at least two new projects exploring the intriguing relationship between adult-generated hippocampal neurons and behaviors relevant to addiction. As these studies hold great potential to improve our understanding of the complex mechanisms by which drugs of abuse affect brain function, they therefore may open new avenues for treatment of addiction and relapse to drug seeking. As these studies also will also shed much-needed light on how adult-generated neurons influence complex behavior - such as drug/context association, extinction from drug-seeking, and behavioral response to stress - they will be important to future efforts to harness neural stem cells for repair of the injured, even addicted, brain and to our understanding of what new neurons can/will do in the adult brain.